Cognition Therapeutics: FDA clears IND for Oral CT1812 for geographic atrophy

CT1812 is an experimental orally delivered small molecule designed to penetrate the blood-brain and blood-retina barriers and bind selectively to the sigma-2 (σ-2) receptor complex. (Image Credit: AdobeStock/wladimir1804)

Cognition Therapeutics announced today its Investigational New Drug (IND) application for the investigation of CT1812 for geographic atrophy (GA) secondary to dry age-related macular degeneration (dry AMD) has been cleared by the FDA.

In a news release, the company said it plans to initiate the Phase 2 MAGNIFY trial of its oral drug candidate, CT1812 in 2023 in individuals with dry AMD who have measurable GA.

Anthony Caggiano, MD, PhD, the company’s chief medical officer and head of research and development, noted in the release that the company enjoyed a collaborative dialogue with the ophthalmology division of the FDA during its pre-IND meeting and are looking forward to assess the potential of CT1812 to impact GA and slow the decline in visual acuity in people with dry AMD.

"We believe that CT1812's oral systemic delivery combined with its potential to protect the retinal pigment epithelium (RPE) from damage in both the affected and fellow eyes, may represent a significant advantage to the millions of people with dry AMD who are at risk for permanent vision loss,” Caggianosaid in the release.

According to the company, the MAGNIFY study (COG2201) is a randomly assigned, placebo-controlled phase 2 trial expected to enroll approximately 246 people who have been diagnosed with dry AMD with measurable GA. Over the treatment period, change in GA lesion size and best-corrected visual acuity, as well as other measures of safety and efficacy will be assessed to determine if treatment can slow vision loss.

“Expansion of our pipeline programs into GA is an excellent example of how we are leveraging our scientific expertise to tackle some of the most challenging diseases,” Lisa Ricciardi, president and CEO of Cognition, said in the release. “Looking ahead, I’m excited by our continued clinical progress as we advance CT1812 through ongoing studies and now into this new indication.”

About CT1812

The company noted that CT1812 is an experimental orally delivered small molecule designed to penetrate the blood-brain and blood-retina barriers and bind selectively to the sigma-2 (σ-2) receptor complex. The σ-2 receptor complex is involved in the regulation of key cellular processes such as membrane trafficking and autophagy that are damaged by toxic interaction with soluble beta amyloid (Aβ) oligomers, oxidative stress and other stressors. Such damage to sensitive cells in the central nervous system (CNS) such as neurons and RPE cells can progress to a loss of function. In dry AMD, this can result in a loss of visual acuity and eventual vision loss.

Early proof-of-concept studies with CT1812 indicate a role of σ-2 receptor modulators in rescuing sensitive RPE cells from damage by stressors such as pathogenic proteins and oxidative stress, thus preserving this crucial component of the macula.

According to the news release, in addition to Cognitions’ new Phase 2 MAGNIFY clinical trial, CT1812 is being studied in a trio of Phase 2 clinical trials: the SEQUEL study, which recently concluded enrollment of adults with mild-to-moderate Alzheimer’s disease; the SHINE study in individuals with mild-to-moderate Alzheimer’s disease; and the SHIMMER study in individuals with dementia with Lewy bodies. CT1812 has not been approved by the FDA or other regulatory agency.